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Association of Gut Microbiota and Metabolites With Disease Progression in Children With Biliary Atresia
Frontiers in Immunology ( IF 7.3 ) Pub Date : 2021-09-23 , DOI: 10.3389/fimmu.2021.698900
Wei Song 1, 2 , Li-Ying Sun 1, 2, 3 , Zhi-Jun Zhu 1, 2 , Lin Wei 1, 2 , Wei Qu 1, 2 , Zhi-Gui Zeng 1, 2 , Ying Liu 1, 2 , Hai-Ming Zhang 1, 2 , Wei Guo 4
Affiliation  

Background and Aims

Biliary atresia is the most common cause of liver disease and liver transplantation in children. The accumulation of bile acids in hepatocytes and the stimulation of the intestinal microbiome can aggravate the disease progression. This study investigated changes in the composition of the gut microbiota and its metabolites in biliary atresia and the possible effects of these changes on disease progression.

Methods

Stool samples of biliary atresia at different disease stages and matched control individuals were collected (early stage: 16 patients, 16 controls; later stage: 16 patients, 10 controls). Metagenomic sequencing was performed to evaluate the gut microbiota structure. Untargeted metabolomics was performed to detect and analyze the metabolites and bile acid composition.

Results

A disturbed gut microbiota structure occurred in the early and later stages of biliary atresia. Klebsiella, Streptococcus, Veillonella, and Enterococcus have always been dominant. The abundance of V. atypica displayed significant changes between the early and later stages of biliary atresia. Combined with clinical indicators, Spearman’s analysis showed that Klebsiella and Veillonella atypica strongly correlated with liver enzymes. Enterococcus faecium had an enormously positive relationship with lithocholic acid derivatives. Metabolites involved in tryptophan metabolism were changed in the patients with biliary atresia, which had a significant association with stool V. atypica and blood total bilirubin (p < 0.05).

Conclusions

The liver damage of biliary atresia was directly or indirectly exacerbated by the interaction of enriched Klebsiella (K. pneumoniae), Veillonella (V. atypica), and Enterococcus (E. faecium) with dysmetabolism of tryptophan and bile acid.



中文翻译:

胆道闭锁儿童肠道微生物群和代谢物与疾病进展的关联

Background and Aims

胆道闭锁是儿童肝病和肝移植最常见的原因。胆汁酸在肝细胞中的积累和肠道微生物组的刺激会加剧疾病的进展。本研究调查了胆道闭锁中肠道微生物群组成及其代谢物的变化,以及这些变化对疾病进展的可能影响。

Methods

收集不同疾病阶段胆道闭锁的粪便样本和匹配的对照个体(早期:16 例患者,16 例对照;晚期:16 例患者,10 例对照)。进行宏基因组测序以评估肠道微生物群结构。进行非靶向代谢组学以检测和分析代谢物和胆汁酸组成。

Results

在胆道闭锁的早期和晚期阶段,肠道菌群结构受到干扰。 克雷伯氏菌, 链球菌, 韦洛内拉, 和 肠球菌一直占主导地位。丰富的V. 非典型在胆道闭锁的早期和晚期之间显示出显着的变化。结合临床指标,Spearman 的分析表明,克雷伯氏菌异型韦永菌 与肝酶密切相关。 屎肠球菌与石胆酸衍生物有极大的正相关关系。胆道闭锁患者参与色氨酸代谢的代谢物发生变化,与大便呈显着相关V. 非典型 和血液总胆红素(p < 0.05)。

Conclusions

胆道闭锁肝损害直接或间接因富集的相互作用而加重。 克雷伯氏菌 (肺炎克雷伯菌), 韦洛内拉 (V. 非典型), 和 肠球菌 (屎肠球菌) 色氨酸和胆汁酸代谢障碍。

更新日期:2021-09-23
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